ALTERNATE PATHWAYS OF BILIRUBIN METABOLISM: 1. To determine the bilirubin dervatives (or heme derivatives) formed in: a. Complete deficiency of bilirubin conjugation (the Gunn rat). b. Phototherapy of the Gunn rat and jaandiced newborn infants. c. Unstable hemoglobinopathies with Heinz-body formation. d. Drug-induced porphyria due to allyl-isopropyl-acetamide. 2. To determine: the subcellular fractions and enzymes in rat liver involved in the alternate pathways of bilirubin metabolism under a & b above, effects on bilirubin metabolism in the Gunn rat of various inducers and inhibitors of microsomal hydroxylation and lysosomal peroxidation. EFFECTS OF PHOTOTHERAPY: 1. To determine the effects of phototherapy on the activity of various hepatic drug metabolizing enzymes, and on its content of cytochrome P450. 2. To determine, by means of freeze-thaw techniques and gel filtration chromatography of Gunn rat bile, whether phototherapy enhances the excretion of unconjugated bilirubin via formation of complexes with other photoproducts. 3. To determine whether the stimulatory effect of phototherapy on bile acid turnover is due to selective alterations of the plasma-tissue pool, as opposed to the enterohepatic pool of bile acids. FORMATION OF PIGMENT GALLSTONES: 1. To identify the insoluble black pigment in pigment gallstones. 2. Develop a chromatographic method for isolation of conjugated bilirubin. 3. Determine the effects of lecithin and calcium on bilirubin solubitity in bile. 4. To determine if hepatobiliary beta-glucuronidase can hydrolyze conjugated bilirubin in bile at the physiological p G values of 7.0-7.8. BIBLIOGRAPHIC REFERENCES: Boonyapisit S.T., Trotman B.W., Ostrow J.D., Gallo D: Measurement of conjugated and unconjugated bilirubin in bile. A new thin-layer chromatographic method. J. Lab. Med., 1976. Knodell R.G., Cheney H.C., Ostrow J.D.: Effects of phototherapy on hepatic excretory function in human alcoholic cirrhosis. Gastroenterology, 1976.